Long-term follow-up of Ta transitional cell carcinoma of bladder after treatment of TURBt plus intravesical therapy

To stduy the association between the prognosis of Ta transitional cell carcinoma (TCC) of the bladder and risk-related factors.Methods A total of 88 cases (62 males and 26 females;mean age,61 years;age range,41-81 years) of initial T.TCC of the bladder treated with transurethral resection of bladder tumor (TURBt) plus intravesical chemotherapy or immunotherapy were enrolled.Among them,there were 26 cases of G1,61 cases of G2 and 1 case of G3.For tumor site,62 cases (16 cases of G1,45 of G2,1 of G3) had single tumor and 26 cases (10 cases of G1,16 of G2) had multi-site tumors.The mean follow-up was 113 months (range,56-168 months).The tumor grade,original tumor number and their association with the recurrence and progression of this type of TCC were retrospectively analyzed.Results The overall recurrence rate (RR) was 60% (53/88).In single tumor group,RR of G1 cases was 25% (4/16);RR of G2 cases was 62% (28/45) and the total RR was 52% (32/62).In multi-site tumor group,RR of G1 cases was 80% (8/10),RR of G2 cases was 75% (12/16) and the total RR was 77% (20/26).The RR of multi-site tumor group was significantly higher than that of single tumor group (P<0.01).In single tumor group,RR of G2 cases was significantly higher than that of G1 cases (P<0.001).In multi-site tumor group,there was no association of RR with tumor grade.There was no progression in G1 tumor cases.The progression rate was 42.5% (17/40) in G2 tumor cases;among them,30% (12/40) progressed to T1G2 tumors and 12.5% (5/40) progressed to T2G2 tumors.The RR of cases who received thiotepa,mitomycin and BCG were 75% (12/16),68% (30/44) and 40% (11/27),respectively.Tumor specific mortality was 1.14% (1/88,a T2G3 case).Conclusion The multi-site Ta TCC of the bladder has relatively higher RR and greater chance of progression after the treatment of TURBt plus intravesical chemotherapy or immunotherapy,especially in the poor differentiated tumors,thus active treatment and close follow-up are essential in clinical practice.9 refs.

Survivin mRNA expression in urine as a biomarker for patients with transitional cell carcinoma of bladder

Transitional cell carcinoma （TCC） of bladder is the most common malignant tumor in uropoiesis system. Up to date, there is still lack of an ideal marker for the diagnosis of TCC except CT and MRI imaging and cystoscopy. Cystoscopy is an invasive examination, which increases the possibility of urinary tract infection. Urine cytology has low sensitivity （21%--40%） in diagnosis of bladder cancer, especially for those with medium or high differentiation. The specificity is often affected by factors such as specimen collection, urinary tract infection, etc. Detecting the expression of survivin mRNA in urine by real time-PCR is simple in specimen collection and is sensitive and relatively specific, which provides a simple and noninvasive diagnostic method for TCC. Moreover it allows comparing the gene expression levels at different stages and grades of TCC, which can help define malignancy degree of TCC.

Mutational analysis of Ras hotspots in patients with urothelial carcinoma of the bladder

BACKGROUND Mutational activation of Ras genes is established as a prognostic factor for the genesis of a constitutively active RAS-mitogen activated protein kinase pathway that leads to cancer.Heterogeneity among the distribution of the most frequent mutations in Ras isoforms is reported in different patient populations with urothelial carcinoma of the bladder(UCB).AIM To determine the presence/absence of mutations in Ras isoforms in patients with UCB in order to predict disease outcome.METHODS This study was performed to determine the mutational spectrum at the hotspot regions of H-Ras,K-Ras and N-Ras genes by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)and DNA sequencing followed by their clinical impact(if any)by examining the relationship of mutational spectrum with clinical histopathological variables in 87 UCB patients.RESULTS None of the 87 UCB patients showed point mutations in codon 12 of H-Ras gene;codon 61 of N-Ras gene and codons 12,13 of K-Ras gene by PCR-RFLP.Direct DNA sequencing of tumor and normal control bladder mucosal specimens followed by Blastn alignment with the reference wild-type sequences failed to identify even one nucleotide difference in the coding exons 1 and 2 of H-Ras,NRas and K-Ras genes in the tumor and control bladder mucosal specimens.CONCLUSION Our findings on the lack of mutations in H-Ras,K-Ras and N-Ras genes could be explained on the basis of different etiological mechanisms involved in tumor development/progression,inherent genetic susceptibility,tissue specificity or alternative Ras dysfunction such as gene amplification and/or overexpression in a given cohort of patients.

Expression and clinical implication of PRL-1 and PRL-3 in transitional cell carcinoma of bladder

The mRNA and protein expression of phos-phatase of regenerating liver 1(PRL-1)and phosphatase of regenerating liver 3(PRL-3)in transitional cell carcinoma of bladder(BTCC)and normal epithelia of bladder was investigated,and the relationship between the BTCC and pathological changes was clarified.The expression of PRL-1 and PRL-3 mRNA was detected by using reverse transcription polymerase chain reaction(RT-PCR)in 30 cases of BTCC and 10 cases of normal bladder,and the expression of PRL-1 and PRL-3 protein was checked by using immunohistochemistry in 30 cases of BTCC and 15 cases of normal bladder.The expression levels of PRL-1 and PRL-3 mRNA and protein were higher in BTCC than those in normal bladder epithelia(P<0.05).The increased expression of PRL-1 and PRL-3 mRNA and protein was detectable in deep invasion and metastasis of BTCC(P<0.05).There was no correlation between the expres-sion of PRL-1 and PRL-3 and gender,age or recurrence of BTCC(all P>0.05).A significantly positive correlation was found between PRL-1 and PRL-3 in BTCC(P<0.05).PRL-1 and PRL-3 are expressed consistently and may contribute to the growth,differentiation,invasion and metastasis of BTCC.

Impact of surgery and epirubicin intravesical chemotherapy on peripheral blood dendritic cell subsets in patients with superficial urothelial carcinoma of the bladder

Background Superficial urothelial carcinoma （SUC） of the bladder is a common urinary tract tumor in China. There is a high recurrence rate of this tumor even after surgery and intravesical instillation. Previous reports have described a suppression of the immune system in cancer patients. Dendritic cells （DCs） play a pivotal role in the induction of an effective antitumor immune response. The aim of this study was to investigate the effects of surgery and epirubicin intravesical chemotherapy （IC） on peripheral blood DCs in subsets of patients with bladder SUC. Methods A total of 66 SUC patients and 38 healthy controls were enrolled in this study. All the patients had undergone transurethral resection （TUR） of their cancer and adjunctive IC after tumor removal. The patients were divided into a non-recurrence group （n=40） and a recurrence group （n=26） based on the presence or absence of tumor recurrence. Blood samples were taken preoperatively （PreOP）, on postoperative days （POD） 1 and 7, and at postoperative month （POM） 3. Flow cytometric analysis was used for the determination and quantitation of the surface markers CD80 and CD86 in circulating DC subsets. Results The preoperative percentages of myeloid dendritic cells （mDCs） and expression of CD80 and CD86 were impaired in SUC patients compared to healthy controls （P 〈0.05）. The percentages of mDCs and these surface markers decreased significantly on POD 1 and increased on POD 7, remaining higher than the preoperative values in POM 3 （P 〈0.05）. The percentages of mDCs, and CD80 and CD86 in the non-recurrence group on PreOP, POD 7, and POM 3 were higher than those in recurrence group. Conclusions Surgical removal of SUC and adjunctive IC were associated with improved circulating mDC counts and function. Persistent depression of mDC counts and function after treatment in recurrence patients indicated lower antitumor immunity that may lead to tumor recurrence.